Royal Decree 1344 / 2007 Of 11 October, Which Regulates Pharmacovigilance Of Medicinal Products For Human Use.

Original Language Title: Real Decreto 1344/2007, de 11 de octubre, por el que se regula la farmacovigilancia de medicamentos de uso humano.

Subscribe to a Global-Regulation Premium Membership Today!

Key Benefits:

Subscribe Now for only USD$20 per month, or Get a Day Pass for only USD$4.99.
This Royal Decree develops the chapter VI of title II of law 29/2006, of July 29, guarantees and rational use of medicines and sanitary products, which establishes guarantees of monitoring of the relationship benefit in drugs and regulates, therefore, the Spanish system of pharmacovigilance and the pharmacovigilance of the medicinal products for human use.
In addition, with this Royal Decree is updated and adapted to technical progress the regulation until now existing in this area, collected in the Royal Decree 711/2002, 19 July, which regulates pharmacovigilance of medicinal products for human use, which is now repealed, and incorporated into the domestic legal order the novelties introduced by Directive 2004/27/EC the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC, which establishes a Community code relating to medicinal products for human use.
The novelties introduced in the title IX 'Pharmacovigilance' of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001, are the result of changes resulting from the international harmonisation of definitions, terminology and technological development, which requires systems of pharmacovigilance in the EU to permanently adapt to scientific and technical progress.
These innovations which introduces the new European regulations and making own this Royal Decree, include the requirement of electronic notification of adverse reactions between the different agents (pharmaceutical industry, national agencies and European Medicines Agency), in order to make possible the creation and maintenance of a European database of suspected adverse reactions, which will manage the European Medicines Agency ensuring its accessibility to the Member States. We should also highlight the introduction of the concept of risk management, meaning the activity planning of pharmacovigilance intended to anticipate the problems of safety of medicines, as well as the introduction of measures that minimize known risks of medications and allow its effective communication, with special mention to Pharmacoepidemiology and, in particular , posautorización studies which should help identify and characterize the risks of drugs and assess the effectiveness of these measures of minimization of risks. Is important, also, the modification of the definitions of 'risks associated with the use of medicines' and 'balance or relationship benefit', which are reflected in this provision.
Finally, should highlight Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004, incorporating a new article 102 bis to Directive 2001/83/EC, the European Parliament and of the Council of 6 November 2001, whereby the control of authorities on the management of the funds destined to the pharmacovigilance activity is imposed the operation of networks of communication and the market, as a fundamental guarantee to preserve its independence, what is already working in Spain and should be moved to the field of Pharmacoepidemiology, so that, with the necessary independence, studies that are of particular interest to protect the public's health are conducted from the public sector.
Taking into account this background, in this Royal Decree are determined, firstly, the agents involved the Spanish pharmacovigilance system of medicinal products for human use, as well as the obligations of each of the agents involved in this activity, which aims to provide the best possible information about the safety of the drugs on an ongoing basis, in order to make possible the adoption of appropriate measures to ensure , so that the drugs available in the market have a relationship benefit for the population in the authorized conditions of use. For the exercise of the pharmacovigilance of medicinal products for human use, the Commission has prepared and published the guidelines contained in the volume 9A of the rules on drugs in the European Union which shall apply, as well as its subsequent updates.
Second, establish administrative consequences that can affect the conditions of authorisation of marketing of drugs for human use for safety reasons, and finally, post-authorisation studies are regulated to the benefit of the authorised medicinal product assessment is continuous.
In the elaboration of this provision have been heard the sectors concerned and consulted the autonomous communities.
This Royal Decree, which has the status of legislation on pharmaceutical products in accordance with article 149.1.16. ª of the Constitution, incorporated into the domestic legal order 1.i paragraphs) and 72 to 76 of article 1 of Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC, which establishes a Community code relating to medicinal products for human use.
In his virtue, a proposal from the Minister of health and consumption, with the prior approval of the Minister of public administration, in accordance with the Council of State and after deliberation by the Council of Ministers at its meeting of October 11, 2007, D I S P O N G O: chapter I General provisions article 1. Scope of application.



The provisions of this Royal Decree are applicable to the pharmacovigilance of medicinal products for human use, as activity of public health which aims the identification, quantification, evaluation and prevention of the risks associated with the use of drugs once marketed.



Article 2. Definitions.



A_efectos_de this Royal Decree, means: to) Spanish system of pharmacovigilance of medicinal products for human use: decentralized structure, coordinated by the Spanish Agency of medicines and health products, which integrates activities that health authorities carried out permanently and continued to collect, develop and, where appropriate, processing the useful information for the supervision of drugs and in particular, information on adverse reactions to medicines, as well as for the realization of many studies are considered necessary to assess the safety of the drugs.



(b) spontaneous reporting program: pharmacovigilance method based on communication, collection and evaluation of reports of suspected adverse drug reactions.
(c) adverse reaction: any response to a medicinal product which is noxious and unintended and which occurs at doses that are normally applied in man for the prophylaxis, diagnosis or treatment of disease or for the restoration, correction or modification of physiological functions. This term also includes all adverse clinical consequences arising from dependence, abuse and misuse of medicines, including those caused by use outside authorised conditions and those caused by medication errors.
(d) serious adverse reaction: an adverse reaction which results in death, may endanger the life, requires the hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or a disability, or is a congenital anomaly or birth defect. For the purposes of notification, be discussed also how serious those adverse reaction suspected to be important from a medical point of view, although they do not meet the above criteria, as those that endanger the patient or require intervention to prevent one of the previous outcomes. Likewise, for the purpose of notification, are they dealt serious all suspicions of transmission of an infectious agent through a drug.
(e) unexpected adverse reaction: an adverse reaction whose nature, severity or consequences is not consistent with the information described in the datasheet.
(f) periodic safety report: document prepared by the holder of the marketing authorisation in accordance with the guidelines established in this regard in the European Union, whose purpose is to update the security information of the drug which, among other things, contains information on suspected adverse reactions that have knowledge in the reference period, as well as a scientific benefit of the medication balance assessment.
(g) post-authorisation study: any clinical or epidemiological study conducted during the commercialisation of a medicine according to the conditions approved on your datasheet or in normal conditions of use, in which the drug or drugs of interest are investigated fundamental exposure factor. This study may take the form of a clinical trial or an observational study.
(h) study posautorización of safety: study pharmacoepidemiological or clinical trial carried out in accordance with the provisions of the marketing authorization, conducted with the purpose of identify, characterize and quantify the risks associated with the authorized medicinal products.
(i) abuse of a drug: excessive and voluntary, persistent or sporadic, use that can result in physical or psychological harm.
(j) yellow card: form for the reporting of suspected adverse reactions, distributed by the competent bodies on pharmacovigilance of the autonomous communities to health professionals.
(k) Good Pharmacovigilance Practices: set of standards or recommendations to ensure: 1 the authenticity and quality of the data collected on pharmacovigilance, allowing to assess at any time the risks associated with the use of drugs;



2nd the confidentiality of information relating to the identity of patients and healthcare professionals;
3 the use of homogeneous criteria in the management of pharmacovigilance information.



(l) risks associated with the use of the medicinal product: any risk to public health or the health of the patient related to the quality, safety and efficacy of the medicinal product; as well as any risk of undesirable environmental effects.



(m) balance or relationship of the drug benefit: evaluation of the favorable therapeutic effects of the medicinal product in relation to the risks associated with their use.
n) risk management Plan: document in which the applicant or the marketing authorisation holder specifies important medication, identified or potential risks, and says security not available relevant information; It establishes a plan for the implementation of pharmacovigilance activities necessary in order to identify them, characterize them or quantify them; (e) includes, where necessary, a specific programme of prevention or minimization of risks, including the activities of training and information professionals and users in the context of this plan and the evaluation of the effectiveness of the measures taken.
n) medication Error: failure by action or omission in the process of treatment with drugs that cause or may cause damage to the patient. Medication errors that may cause damage to the patient will be considered for purposes of reporting adverse reactions, except those derived from the therapeutic failure by omission of a treatment.



Article 3. Sources of information on pharmacovigilance.



1 information about the risks associated with the use of drugs can come from the following sources: a) spontaneous reporting individual cases of suspected adverse reactions by health professionals.



(b) studies posautorización.
(c) databases sanitary computerized.
(d) Preclinical data of animal experimentation.
(e) information on the clinical trials of a drug.
(f) information related to manufacturing, conservation, sale, distribution, dispensing, prescribing and use of drugs.
(g) scientific publications.
(h) other sources of information, as misuse and abuse of drugs, or those corresponding to medication errors, which can provide data relevant to the assessment of the benefits and risks of medicines.
(i) other health authorities and international health organizations.



((2. the Spanish Agency for medicines and health products will establish the necessary agreements with the competent bodies of the autonomous communities for the sharing of sources of information that they depend on mentioned in paragraphs c), f) and h) of the previous paragraph.



3. in order to facilitate the exchange of information on individual cases of suspected adverse reactions, apply the guidelines developed and issued by the European Commission in volume 9A of the rules on medicinal products in the European Union, concerning the collection, verification and presentation of notifications of adverse reactions, including technical requirements for electronic exchange of pharmacovigilance information According to the formats agreed upon internationally and on internationally accepted medical terminology.



Chapter II of the Spanish pharmacovigilance system of medicinal products for human use article 4. Agents of the Spanish pharmacovigilance system of medicinal products for human use.



1 the Spanish pharmacovigilance system of medicinal products for human use is integrated by: a) the Spanish Agency of medicines and health products, which acts as Coordinator.



(b) the competent bodies pharmacovigilance of the autonomous communities and the units or regional pharmacovigilance centres attached to them.
(c) health professionals.



2. the Technical Committee of the system Spanish pharmacovigilance of medicinal products for human use, as a coordinating body made up of the Spanish Agency of medicines and health products and competent pharmacovigilance of the autonomous communities, or units who delegated, it will unify the operation of spontaneous reporting program criteria, will evaluate the alert signals generated by the Spanish pharmacovigilance system of medicinal products for human use and discuss the methodological and practical aspects of few studies intends to make in its bosom.



Article 5. Functions of the Spanish Agency of medicines and health products pharmacovigilance of medicinal products for human use.



1 the functions of the Spanish Agency of medicines and health products are: a) coordinate and evaluate the Spanish pharmacovigilance system of medicinal products for human use, as well as to carry out the tasks of secretariat of its technical Committee, in accordance with the «good practices of pharmacovigilance of the system Spanish of pharmacovigilance of medicinal products for human use"drawn up by the Technical Committee and published by the Ministry of health and consumption. Also is responsible for planning and development of such system in relation to the autonomous communities.



In exercise of its powers of coordination, the Spanish Agency of medicines and health products will oversee the permanence and continuity of the program of spontaneous reporting in the respective autonomous communities, and shall submit an annual report of activities of the Spanish pharmacovigilance system of medicinal products for human use to the Security Committee of drugs for human use.
(b) establish, in collaboration with the autonomous communities, a network of data allowing the competent organs in pharmacovigilance of the autonomous communities, or units in which delegated, have accessible telematics all the information collected by the Spanish pharmacovigilance system of medicinal products for human use.
(c) to manage the database of the system Spanish of pharmacovigilance of medicinal products for human use, ensuring at all times their availability and updating, monitoring their safety and ensuring data confidentiality and integrity for data transfer processes. The Ministry of health and Consumer Affairs shall establish the terms in which this information will be made available to the public.
(d) acting as a focal point of the Spanish pharmacovigilance system of medicinal products for human use with drugs marketing authorisation holders and with international bodies, without prejudice to competences in pharmacovigilance of the autonomous communities.
(e) immediately available to the marketing authorisation holder, and in any event within fifteen calendar days following its receipt, notifications about suspected adverse reactions serious that have occurred in Spain and in which are involved as suspected drugs which are holders.
Any other information concerning pharmacovigilance not referred to in the previous paragraph will have to be expressly requested by the person concerned, in accordance with the procedure laid down for that purpose.
f) transmit to the European Medicines Agency and the other Member States immediately, and in any event within fifteen calendar days following its receipt, notifications about suspected adverse reactions serious have occurred in Spain.
Such communication shall be effected through the network of data processing to the European Medicines Agency established in collaboration with the Member States and the European Commission.
(g) promote the creation of database health computerized which serve as source of information for studies Pharmacoepidemiologic with the participation of the health authorities of the autonomous communities and health professionals.
(h) promote and realize the Pharmacoepidemiology studies necessary to evaluate the safety of approved drugs.
(i) assess the information received from the Spanish pharmacovigilance system, as well as other sources of information. In particular, the Agency will assess the information from periodic safety reports, plans risk management and post-authorisation studies that have implications on the safety of drugs.
(j) establish appropriate measures to manage the identified risks, including the training and information, with the ultimate goal of minimizing them or prevent them.
(k) ensure public access to the information sent by the marketing authorisation holders or by any other entity or person deemed especially relevant to the protection of public health.
(l) establish, together with the autonomous communities, the relevant inspection procedures that ensure compliance with the obligations of marketing authorisation holders indicated in article 8.
(m) any other function that may be necessary in the field of pharmacovigilance, and that should be exercised by the Spanish Agency of medicines and health products.
2. the Spanish Agency for medicines and health products will ensure, in their sphere of competence, the necessary means to carry out the pharmacovigilance and risk management, as well as independent studies that were accurate to assess the safety of the drugs.



Article 6. Participation of the autonomous communities in the Spanish pharmacovigilance system of medicinal products for human use.



1. the programs of spontaneous reporting that the autonomous communities will develop continuously and permanently will be adapted to good practices of pharmacovigilance from the Spanish pharmacovigilance system of medicinal products for human use to be published by the Ministry of health and consumption.



2. the autonomous communities registered in the database of the Spanish system of pharmacovigilance notification of suspected serious adverse reactions within a maximum of 10 calendar days from the receipt of the information.
The Spanish Agency of medicines and health products may require the health authorities of the autonomous communities the information required to assess the safety of the drugs.
3. the autonomous communities shall co-operate with the Spanish Agency of medicines and health products for the implementation and development of programmes and studies on the evaluation and risk management of medicines, in accordance with decisions adopted by the Committee of safety of medicines for human use and by the Spanish Technical Committee of pharmacovigilance of medicinal products for human use.
4. the autonomous communities and the Spanish Agency of medicines and health products shall cooperate in the dissemination of knowledge about the safety of the drugs in the health care field.



Article 7. Obligations of health professionals.



Health physicians, pharmacists, dentists, nurses and other professionals have an obligation of: to) notify suspicions of adverse reaction of the authorized medicinal products, including those that have been used in conditions other than those authorized and drugs not marketed in Spain but that have authorized import according to article 24.4 of law 29/2006 , 26 July. These notifications will be sent as soon as possible to the competent body for pharmacovigilance of the autonomous community corresponding to the fields of healthcare, through the collection of suspected adverse reactions form ('yellow card').



Priority will be given to the notification of serious or unexpected adverse reactions of any medications and those related to the new drugs identified by the yellow triangle described in article 8.2.
When suspicions of adverse reaction arising from failure of medication, according to the definition that appears in the article 2.n), the notification can be made according to special procedures to be agreed by the Technical Committee of the Spanish system of pharmacovigilance and that will be reflected in the document of «Good practices of pharmacovigilance from the system Spanish of pharmacovigilance of medicinal products for human use».
(b) retain the clinical documentation of the suspected adverse reactions to drugs, in order to complete or to track, if necessary.
(c) cooperate with the Spanish pharmacovigilance system of medicinal products for human use, providing the necessary information that they are requested to identify, characterize and quantify reactions adverse or to expand or complete information about suspected reactions reported adverse.
(d) be informed about the safety data on drugs that usually prescribe, dispense or administer, and carry out in their fields of healthcare measures of prevention of risks that settle down in the datasheet of the medication, including training and informational measures users.
(e) collaborate with management of risks, in particular in qualified drug plans as of special medical supervision.
(f) collaborate with responsible for pharmacovigilance of holders of marketing authorisations, where a suspected adverse reaction to one of its drugs, providing the information required for subsequent notification to the Spanish pharmacovigilance system by licensee.
(g) collaborate, as experts, with the Spanish Agency of medicines and health products and the competent bodies of the autonomous communities, in the evaluation of the problems of safety of medicines for human use.



Chapter III article 8 marketing authorisation holders. Obligations of the holder of the marketing authorisation.



1 the holder of the marketing authorization, in accordance with the «good practices of pharmacovigilance of medicinal products for human use for the pharmaceutical industry", published by the Ministry of health and consumption, must: to) keep detailed records of all suspected adverse reactions occurring in Spain, the European Union or a third country. (Except in exceptional circumstances, such as the technical impossibility, suspicions of individual cases of adverse reactions which meet the criteria set out in paragraphs b) g), shall be sent by electronic means in accordance with the guidelines contained in the volume 9A of the rules on medicinal products in the European Union. According to these guidelines, marketing authorisation holders shall use internationally accepted medical terminology.



(b) record and report suspected serious adverse reactions that occurred in Spain to the competent body for pharmacovigilance of the autonomous community which exercised their activity the healthcare professional who has reported the case. Such notification must be immediately, and in any case within 15 calendar days following the receipt of the information. Be both reported suspicions of serious adverse reactions associated with authorized medicinal products, including those that have been used in conditions other than those authorized, such as those associated to drugs not marketed in Spain but that have authorized import according to article 24.4 of the law 29/2006, of July 26. It shall also notify any other suspected serious adverse reactions occurring in Spain and which may be expected reasonably to have knowledge.
If the communication is made on paper be used any of the official languages of the corresponding autonomous community.
Where the notification is made in European standard electronic format, this will be directly to the network of data of the Spanish pharmacovigilance system of medicinal products for human use, referred to in article 5.1. b), according to the standards of the European Union, including the narration of the case, which must be in the official language of the State and shall include a translation into the English language. The Spanish Agency of medicines and health products will promptly publish guidelines to keep in touch with the electronic notification.
When suspicions of adverse reaction arising from failure of medication, according to the definition that appears in the article 2.n), the notification can be made according to special procedures to be agreed by the Technical Committee of the Spanish system of pharmacovigilance and that will be reflected in the document of «Good practices of pharmacovigilance of medicinal products for human use for the pharmaceutical industry».
c) guarantee that all suspected adverse reactions serious and at the same time unexpected drugs authorized in Spain that occur outside the European economic area, which was aware through a health services professional, are communicated to the Spanish Agency of medicines and health products immediately and in any case within 15 calendar days following the receipt of the information. When the notifications referred to in this paragraph are made to the European standard electronic format, shall be deemed notified Spain all suspected adverse reaction that is sent to the database of the European Medicines Agency, not requiring specific notification to Spain.
(d) to track the scientific literature world, in order to identify the published cases of adverse reactions in which there are reasonable suspicions that the deceased is an active ingredient of a drug whose authorization to market in Spain is holder. (These cases are communicated in accordance with the criteria specified in paragraphs b) and (c)).
((e) ensure that the suspected serious adverse reactions that occur during the course of a post-authorisation study, and which can be expected reasonably have knowledge, they are communicated using the criteria specified in paragraphs b) and (c)) in accordance with the criteria established in the guidelines contained in the volume 9A of the rules on medicinal products in the European Union.
((f) as regards advanced therapy medicines, communication of suspected adverse reactions will take place according to the criteria specified in paragraphs b) and (c)). However, when the suspected adverse reaction involves the transmission of a disease or problem, either by contamination during the process, or because you were already contained in the tissue or cell group, the holder shall endeavour to make the notification to a period not exceeding 48 hours, entering on such communication the European single code of the donation that established the Royal Decree 1301 / 2006 , 10 November, that establish the norms of quality and safety for the donation, obtaining, evaluating, processing, preservation, storage and distribution of human tissues and cells and approve standards coordination and operation for use in humans.
g) ensure, in the case of drugs whose status Member reference is Spain, which has been authorized by decentralised or mutual recognition procedure, or which have been subject to Community decision, that all suspected serious adverse reactions that occur out of Spain but in the territory of the European Union to communicate in the format and at the intervals indicated by the Spanish Agency of medicines and health products for analysis and monitoring of these reactions adverse for the entire European Union. When the notifications referred to in this paragraph are made to the European standard electronic format, shall be considered notified to Spain every adverse reaction that is sent to the database of the European Medicines Agency or the competent authority of the Member State concerned if it occurs within the European Union, not requiring specific notification to Spain.
(h) submit to the Spanish Agency of medicines and health products records of all suspected adverse reactions in a periodic safety report, in accordance with the guidelines contained in the volume 9A of the rules on medicinal products in the European Union.
This presentation must be made immediately at the request of the Spanish Agency of medicines and health products, and, in addition, from time to time pursuant to the terms contained in this paragraph, provided that other requirements have not been established as a condition for granting marketing authorization.
The periodicity of the reporting will be half-yearly upon authorisation and to marketing. Once marketed will be presented every six months during the first two years after the first marketing in any country of the European Union and annually during the next two years. Thereafter the periodic safety report will be presented at three yearly intervals. This periodicity is applicable to all drugs regardless of the date of authorization.
The holder may request the amendment of the periods referred to in the preceding paragraph, together with the request for authorization, or once granted in accordance with the procedure laid down in the rules which regulate the evaluation, registration, authorization and conditions of dispensing of medicaments for human use manufactured industrially.
The circumstances in which is required to restart the periodicity of submission of periodic safety reports are described in volume 9A. In such circumstances if the holder considered that the beginning of the periodicity is not required, you must request an exemption at the time of authorization, or once granted the same according to the procedure laid down in the rules which regulate the evaluation, authorisation, registration and conditions of dispensing of medicaments for human use manufactured industrially. In any case, the start of the periodicity shall be compulsory when adding an indication for Pediatric use of a drug that did not have it.
On the occasion of the renewal of the authorization, the holder of the authorization will follow instructions of volume 9A regarding the presentation of the periodic report of appropriate security.
(i) conduct post-authorisation studies to generate information about the characteristics of the use of medicines, confirm, quantify or characterize potential risks, either to provide new scientific information on the relation benefit of drugs authorized in Spain.
(j) carry out a continuous assessment of the relationship benefit from drugs that have authorized in Spain and immediately communicate any new information that may influence the global assessment benefit or may require the modification of the sheet, prospect or both to the Spanish Agency of medicines and health products.
Additionally, you must inform immediately to the Spanish Agency of medicines and health products any restriction, suspension or prohibition imposed by the competent authorities of any country.
(k) provide a report of the benefit relationship when requested to do so by the Spanish Agency of medicines and health products.
(l) to carry out the plans of pharmacovigilance and risk management that are established, including studies that the competent authorities consider necessary to assess the safety of the drug, or to assess the effectiveness of risk minimization measures for each medication.
(m) not to communicate to the public data on pharmacovigilance issues relating to its authorised medicinal product without that previously has been communicated, at least 24 hours in advance, to the Spanish Agency of medicines and health products. The holder of the marketing authorization shall ensure that the information is presented in a way objectively and is not misleading, and without omitting relevant safety information. The lack of communication to the agency or disseminate the information without respecting the terms provided for in this section shall be considered as a breach of the duty of pharmacovigilance laid down in article 101.2. b. 14) of law 29/2006, of July 26. The Agency shall take the necessary measures to ensure the fulfilment of this obligation.
(n) carry out in Spain the regulatory measures taken for reasons of safety for drugs which is holder, as well as all the measures and studies included in the risk management plan and which have to be performed in Spain.
(n) establish procedures so that medical visitors comply with the duty to notify them all information relating to the use of drugs whose promotion deal, especially indicating adverse reactions that visited people report to them.



2. for medicinal products containing active ingredients not previously authorized in Spain, the holder shall be obliged to include in all catalogues, promotional materials and any other type of material for dissemination to health professionals, the pictogram indicated in annex, during the first five years since its approval. For drugs with active substances already authorised, the pictogram will appear until the first met five years since the approval of the first drug that contains them.



When relevant modifications that may affect the safety profile of the drug, such as new ways of management, new combinations, new indications for different populations to the common, and any others by reasoned decision of the Spanish Agency of medicines and health products, this may set a longer period.
3 this article shall not apply to holders of authorisation of homeopathic medicinal products registered by the special simplified procedure, except for the obligations contained in paragraphs j) and k) of paragraph 1.



Article 9. Person responsible for pharmacovigilance.



1. the holder of the authorization of marketing of a medicinal product for human use must have in Spain, permanent and continuous way of properly qualified as responsible for pharmacovigilance. The holder of the marketing authorization shall communicate to the Spanish Agency of medicines and health products, as well as to the competent organs in pharmacovigilance in the autonomous region where it is situated, the name of this responsible. The Spanish Agency of medicines and health products shall maintain a record of these decision makers.



2 the person responsible for pharmacovigilance shall have the following functions: to) create and maintain a system to collect, treat and assess the information about all suspected adverse reactions reported to the personnel of the company and doctors visitors, so it's accessible at least at one place of the European Union.



((b) prepare and submit periodic safety reports to the Spanish Agency of medicines and health products to which refers article 8.1. h).
(c) make giving an answer quick and complete to any request for additional information from the Spanish Agency of medicines and health products necessary to evaluate the benefits and risks of a drug, including information on the volume of sales or prescriptions of the medicinal product concerned.
(d) facilitate any other information relevant to the evaluation of the benefits and risks associated with a drug, including information on posautorización of safety studies to the Spanish Agency of medicines and health products.
(e) ensure the necessary mechanisms to carry out in Spain the regulatory measures taken for reasons of safety for drugs whose pharmacovigilance is responsible, as well as all the measures and studies included in the risk management plan and which have to be performed in Spain.
(f) Act as point of contact for pharmacovigilance inspections in Spain.



3. the preceding paragraphs shall not apply to holders of authorisation of homeopathic medicinal products registered by the special simplified procedure.



Article 10. Information provided by the holder of the marketing authorisation for security reasons.



1. the holder of the marketing authorisation is required to disseminate to health professionals updated sheet of the medicinal product, together with the information referred to in article 15.2 of law 29/2006, of July 26. In addition, you must make available health administrations sheet authorized by the Spanish Agency of medicines and health products.



2. when at the discretion of the holder of the authorization of marketing or the Spanish Agency of medicines and health products deemed necessary that the first inform healthcare professionals about new data related to the safety of the medication or prevention of risks, and decide to transmit single letter every health professional concerned, the text must be previously agreed with the Spanish Agency of medicines and health products If supplementary material, as well as the shipping schedule and type of healthcare professional that it targets. In all cases shall incorporate into the envelope a hallmark indicating the nature of the information that it contains.



Chapter IV article 11 administrative intervention. Body advice and participation of experts in the evaluation of the safety of the drugs.



1. the Spanish Agency for medicines and health products will be with the Committee of safety of medicines for human use, College laid down in Royal Decree 520/1999 of 26 March, which approves the Statute of the Spanish Agency of medicines and health products, for his advice on pharmacovigilance and whose composition will be made public.



2. the Agency Spanish medicines and sanitary products may request expert advice on safety of medicines and other medical and scientific areas among which will be the technicians of the Spanish pharmacovigilance system of medicinal products for human use designated bodies in each autonomous community.
These experts can evaluate specific problems of security, post-authorisation studies, periodic safety reports, plans for risk management and application for alteration of the technical file.



Article 12. Modification of authorization for reasons of pharmacovigilance.



1. in accordance with article 17.9 of law 29/2006, of July 26, when the holder of an authorization of marketing of a drug know new relevant information affecting the safety of the drug, including its knowledge through circular or individual notification of the Spanish Agency of medicines and health products, you must update without delay record authorization and registration through the procedures of modification of the conditions of authorisation of medicinal products for human use, being its failure cause of suspension or revocation of the authorization. This modification will be subject to the payment of the corresponding fee.



2. when of the evaluation of pharmacovigilance data is infer reasons of public interest, protection of the health or safety of persons, the Spanish Agency of medicines and health products may restrict the conditions of authorisation of a medicinal product, and establish any reservations or scope of use of the same restrictions that are listed below (, as defined in the rules for authorisation, registration and dispensation of medicines for human use industrially manufactured conditions: to) medicine for hospital use (H).



(b) medicine hospital diagnosis or prescription by certain specialists (DH).
(c) special medical monitoring (ECM) medication.



Article 13. Suspension or revocation of the authorization for reasons of pharmacovigilance.



1 the Spanish Agency of medicines and health products, in accordance with the evaluation of pharmacovigilance data, may temporarily suspend or permanently revoke the authorisation of a medicinal product when: a) under normal conditions of use is unfavorable benefit.



(b) for any other reason, suppose a foreseeable risk for the health or safety of persons.
(c () fails to comply with the regulations of pharmacovigilance, in accordance with article 22.1. d) of law 29/2006, of July 26.
The European Medicines Agency had thus agreed to d).



2. for reasons of public health, and until the procedure of suspension or revocation is resolved, may impose the suspension injunction the market through reasoned ruling. In these cases, the person concerned shall withdraw from the market the product at its expense, without prejudice to a performance by the Spanish Agency of medicines and health products when the urgency of the case requires it. Costs that cause these measures shall be borne by the person concerned, without that it has, in any case, sanctioning character.



Article 14. Evaluation and procedure in cases where damages a suspension or revocation of the marketing authorisation or of the authorized conditions of use modification.



1 when, for reasons of the Spanish Agency of medicines and health products pharmacovigilance consider that attends any of the circumstances provided for in the articles 12.2 and 13 as reason for modifying relevant of revocation or suspension of the authorization or the authorized conditions of use, respectively, continue to the following actions: to) the Agency shall ask the holder of the marketing authorisation a report that evaluates the security problem detected and , if any, relationship benefit of medication for conditions of use authorized in Spain, including proposed measures for reducing the risk. This report shall follow the structure and issues that are specified in the request from the Spanish Agency of medicines and health products. The report must be submitted within a maximum period of 60 days from the receipt of the request, unless the urgency of the problem, a period shorter, or in exceptional cases and at the request of the holder is provided by the Agency, a longer period is agreed with the Agency.



(b) in view of the report, the Spanish Agency of medicines and health products shall draw up a report of evaluation of the safety problem.
c) if the earlier report shows the need to adopt a measure of suspension or revocation of the authorization, or modification of conditions of use for security reasons, shall be given ex officio the commencement of the corresponding procedure. In all cases in which a suspension or revocation of the authorization may arise, the Security Committee of medicines for human use shall deliver prescriptive but non-binding opinion.
In specific cases in that game are the interests of the European Union, the Spanish Agency of medicines and health products, or the holder of the marketing authorization may refer the matter to the drug Committee of human use of the European Agency of medicines, for the adoption of a community decision.
(d) after hearing the interested party, will dictate a resolution the remedies and shall be notified to the person concerned. This procedure will be resolved and notify maximum within the period of six months, without prejudice to the interruption of the deadline for the issuance of the report of the Committee of safety medicines for human use, and of the Committee on drugs of use human of the European Medicines Agency, in cases in which the interests of the European Union are at stake , agree article 83.3 of law 30/1992, of November 26, legal regime of public administrations and common administrative procedure.



2. in the case of the modification of the authorisation procedure, the resolution will indicate changes that must be entered on the sheet, prospect, labels and scope of use of the drug, as well as other measures to reduce the risk and inform health professionals and users.



In accordance with these provisions, the holder of the marketing authorization shall request the timely amendment of the conditions of authorisation of the medicinal product, in accordance with the procedures laid down in the regulation, authorisation, registration and dispensation of industrially manufactured medicaments for human use conditions.
3. the procedure laid down in this article shall not apply to medicines authorised through the centralised procedure established by Regulation (EC) No. 726/2004 of the Parliament and of the Council of 31 March 2004, which lays down Community procedures for the authorisation and the control of medicines for human and veterinary use and establishing a European Medicines Agency which will be governed by its specific regulations.



Article 15. Urgent modifications for reasons of security and procedure.
1 when it is becomes aware of new information that indicates a significant risk to human health associated with the use of the drug or have a relevant impact on the safety, the Spanish Agency of medicines and health products may agree the provisional and urgent information change medication that will especially affect any of the following sections of the sheet : indications, posology, contraindications, or warnings and special precautions for use.



2 when the owner needed urgent of the conditions of authorisation of a medicinal product modification for safety reasons, request such modification to the Spanish Agency of medicines and health products, accompanying the following documentation: to) report on detected risks that make necessary modification.



(b) proposal for amendment of the sheet and prospectus.
(c) proposal of information to health professionals and, where appropriate, users.
(d) proposal of complementary actions, as well as any other information deemed necessary for the effective implementation of the modification.



If the Spanish Agency of medicines and health products makes no objection within the next business day upon receipt of the information, the urgent modifications for safety reasons will be considered accepted on a provisional basis. The holder of the marketing authorization shall request the modification of the technical data in a period not exceeding 15 calendar days following the date of acceptance. The Spanish Agency of medicines and health products will establish specific procedures to follow.



3. when the urgent modification for safety reasons come imposed by the Spanish Agency of medicines and health products, the holder shall be obliged to submit an application for modification in the terms that establishes the Agency immediately and within a period not exceeding the 15 calendar days following receipt of the notification of the Agency.
4. in the case of paragraphs 2 and 3, the term and the terms of information directed to health professionals, as well as the effective implementation of the modification by the holder, including changes in packaging material, be agreed with the Spanish Agency of medicines and health products.
5. where in the case of products approved by the decentralised or mutual recognition procedure, the mechanisms of harmonization established for this purpose in the European Union through the corresponding guidelines be taken into account. For products authorised according to the centralised procedure shall be followed as specified in the Commission Regulation (EC) No. 1084 / 2003 Commission of 3 June 2003 concerning the examination of amendments to the terms of authorisations for the marketing of medicinal products for human use and veterinary medicinal products granted by the competent authority of a Member State , and the guidelines that develop it.



Article 16. Communications and measures are precautionary.



1 if the Spanish Agency of medicines and health products, in view of the pharmacovigilance data, considers that a marketing authorisation should be subject to suspension, revocation or modification that involves a relevant restriction of the use of the drug, forthwith to the autonomous communities, to the European Medicines Agency, the other Member States and the marketing authorization holder.



2. in urgent cases, to protect the public health, the Spanish Agency of medicines and health products may suspend the authorization of marketing of a drug informing thereof, later than the first working day following, the ministries of health of the autonomous communities, the European Commission, the European Medicines Agency, the other Member States and the marketing authorization holder.
3. the resolutions of suspension, revocation, and relevant modification of the authorisation, in which may affect public health in third countries, they shall bring to the attention of the World Health Organization.



Article 17. Modification, suspension and revocation of the authorisation of medicines approved by the decentralised and mutual recognition procedures.



1. without prejudice to the provisions of article 14, when the Spanish Agency of medicines and health products, in accordance with the evaluation of pharmacovigilance data, considers necessary for public health reasons, the modification, suspension or revocation of the marketing authorisation of medicinal products authorized by decentralised or mutual recognition procedures, it shall refer the matter to use human of the European Medicines Agency Committee of drugs so that a decision community.



2 notified the Community decision, without any further formality than the audience to the person concerned, the Spanish Agency of medicines and health products will adopt and notify the timely resolution, with an indication of the resources, within the period of 30 days from notification of the Community decision.
3. in cases in which it was justified a suspension injunction of the medication, shall apply the provisions of article 16.2 and shall be informed of the reasons for the suspension, at the latest the day following the adoption of the measure, to the ministries of health of the autonomous communities, the European Commission, to the European Medicines Agency to the other Member States and the marketing authorization holder.



Article 18. Communication to the health professional, autonomous communities and citizens.



1. the Spanish Agency for medicines and health products inform of the autonomous communities and other responsible agencies, concerning the adoption of the measures provided for in this chapter have relevance to public health.



2. the Spanish Agency for medicines and health products and the autonomous communities to be sent to health professionals and citizens, in proper form, information about the risks of drugs.



Chapter V of the studies posautorización article 19. Applicable regime.



1. Post-authorisation studies must have intended complement information obtained during the clinical development of drugs prior to their authorization. Planning, conducting or financing of studies post-authorisation with the purpose of promoting the prescription of drugs is prohibited.



2. health authorities established by common agreement conditions that carry out studies post-authorisation of observational type in order to favour those who can contribute to the knowledge of the drug or to improve clinical practice. The Spanish Agency of medicines and health products will coordinate the actions carried out in this area and establish a post-authorisation studies Coordination Committee with the participation of representatives of all the autonomous communities and the Spanish Agency of medicines and health products, which will discuss the guidelines of the common procedures that each community will run in its area of competence. The functioning of this Committee shall be governed by the rules contained in the law 30/1992, of 26 November, legal regime of public administrations and common administrative procedure, for the colleges.
3. the Agency Spanish medicines and sanitary products will maintain a registry of proposed study post-authorisation of observational type, you will have access the competent bodies of the autonomous communities, and inform each promoter on the procedures to be followed in each case. For this purpose, the promoter of the study shall be sent to the Spanish Agency of medicines and health products the study protocol.
4 when the Studio posautorización, in accordance with the provisions of article 58 of the law 29/2006, of July 26, character of clinical trial and observational study does not, it is not governed by the provisions of this chapter, but it will be implementing Royal Decree 223/2004, of 6 February, which regulates clinical trials of medicinal products for human use.
5. when a post-authorisation of observational type study a condition established in the time of the approval of a drug, either constitutes a requirement for the competent authority to clarify issues relating to the safety of the drug, or part of the plan for managing risks that must carry out the holder only require the authorization of the Spanish Agency of medicines and health products , according to the procedures established for that purpose. The Spanish Agency of medicines and health products of these studies will inform the autonomous communities are where they are to perform and will include them in the registry referred in paragraph 3.
6 when he is promoted by health authorities or publicly funded studies, simplified procedures in order to facilitate their completion shall be established, which will be agreed in the Committee of coordination of studies Posautorización referred to in paragraph 2.
7. the promoter of the study shall notify the autonomous communities where will be the study and the Spanish Agency of medicines and health products the date of the effective start of the study, and shall be sent, where appropriate, the annual monitoring and final reports, as well as the relevant amendments of the Protocol.
8. in any case, the promoter of a post-authorisation safety study shall take into account the guidelines that are collected in the volume 9A of the rules on medicinal products in the European Union.



Sole additional provision. Cities with statute of autonomy.



The references made to the competent organs in pharmacovigilance of the autonomous communities shall be deemed performed also to cities with statute of autonomy, with the coverage provided in their respective statutes of autonomy and Royal Decrees of devolution.



Sole repeal provision. Repeal legislation.



The Royal Decree 711/2002, 19 July, which regulates pharmacovigilance of medicinal products for human use is hereby repealed.



First final provision. Character of legislation.



This Royal Decree is lectures on development of law 29/2006, of July 26, guarantees and rational use of medicines and health products, and has the character of law of pharmaceutical products for the purposes specified in article 149.1.16. ª of the Constitution.



Second final provision. Faculty of development.



It empowers the Minister of health to enact the provisions necessary for the correct application and development of this Royal Decree.



Third final provision. Incorporation of European Union law.



By this Royal Decree 1.i paragraphs are incorporated into the domestic legal order) and 72 to 76 of article 1 of Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC, which establishes a Community code relating to medicinal products for human use.



Fourth final provision. Entry into force.



This Royal Decree shall enter into force the day following its publication in the "Official Gazette".



Given in Madrid, on October 11, 2007.



JUAN CARLOS R.



The Minister of health, BERNAT SORIA ESCOMS annex pictogram that identifies drugs with new active ingredients the pictogram shall consist of an equilateral triangle with the apex upward, black border and a yellow background.




△ This glyph will appear in visible place, to the left of the name of the drug, at least at the top of the information that is supplied, and will be of a similar size to the letter of the name and a minimum of 0.5 cm of side.

Related Laws